The proposed studies are primarily directed at defining the effects of immunosuppressive drugs on lymphocyte numbers and their functional activities. Results are to be correlated with changes in parameters of immunity. One aspect of the investigation concerns an assessment of the activity of various cytotoxic drugs on murine NK cell function and B cell colony formation. In addition, these drugs will be tested for the comparative effects on antibody responses to thymic dependent and independent antigens. Correlative studies using human T cell colony assay will be undertaken in order to evaluate patients with suspected T cell defects. These include those with connective tissue diseases and individuals receiving cytotoxic drug therapy. Another area of study will be directed at the potential therapeutic activities of PGE1 in murine models of SLE. We have shown that this agent markedly prolongs survival in the NZB/W and MRL/1 strains and that these beneficial effects are associated with distinctive lymphoid changes. However, therapeutic activity of this agent is not due to generalized immunosuppression; rather, it appears to selectively inhibit certain immune responses. The latter is manifested by reduction in circulating immune complexes. The relationships between lymphoid changes, parameters of immunity and increased survival will be further evaluated.